Breakthrough blood test brings new hope for early detection of eight common cancers

American researchers have just announced a breakthrough single blood test for eight common cancer types – including “silent killers” like pancreatic and ovarian cancer that currently have no screening tests.

January 19, 2018

American researchers have just announced a breakthrough single blood test for eight common cancer types – including “silent killers” like pancreatic and ovarian cancer that currently have no screening tests.

The test has been developed by Johns Hopkins Kimmel Cancer Center researchers who say the test can also help identify the location of the cancer.

Research on the breakthrough test has just been published online on Science magazine. In a press release the Johns Hopkins researchers say the test, called CancerSEEK, is a unique, non-invasive test that can simultaneously evaluate the levels of eight cancer proteins and the presence of cancer gene mutations from circulating DNA in the blood.

The test is aimed at screening for eight common cancer types that account for more than 60 percent of cancer deaths in the US and a similar percentage in New Zealand. Five of the cancers covered by the test – ovarian, liver, stomach, pancreatic and oesophageal cancers – currently have no screening test.

Four hundred patients of a Melbourne Hospital were part of evaluation of the test’s effectiveness and the Sydney Morning Herald quoted Professor Peter Gibbs, an Australian scientist involved in the research, saying that while a larger study was now underway in the United States – involving 10,000 people – he expected consumer demand would probably be so great that the test would become commercially available before that work was completed.

The test was evaluated on 1,005 patients with nonmetastatic, stages I to III cancers of the ovary, liver, stomach, pancreas, oesophagus, colorectum, lung or breast. The median overall sensitivity, or the ability to find cancer, was 70 per cent and ranged from a high of 98 per cent for ovarian cancer to a low of 33 per cent for breast cancer. For the five cancers that have no screening tests –ovarian, liver, stomach, pancreatic and oesophageal cancers –sensitivity ranged from 69 per cent to 98 per cent. The test was also used on 812 healthy controls and produced only seven false-positive results.

Dr Joshua Cohen, an MD-PhD student at Johns Hopkins University School of Medicine and the research paper’s first author said circulating tumor DNA mutations can be highly specific markers for cancer. “To capitalise on this inherent specificity, we sought to develop a small yet robust panel that could detect at least one mutation in the vast majority of cancers. In fact, keeping the mutation panel small is essential to minimise false-positive results and keep such screening tests affordable.”

The investigators initially explored several hundred genes and 40 protein markers, whittling the number down to segments of 16 genes and eight proteins. They point out that this molecular test is solely aimed at cancer screening and, therefore, is different from other molecular tests, which rely on analysing large numbers of cancer-driving genes to identify therapeutically actionable targets.

In this study, the test had greater than 99 per cent specificity for cancer. “Very high specificity was essential because false-positive results can subject patients to unnecessary invasive follow-up tests and procedures to confirm the presence of cancer,” says Kenneth Kinzler, PhD, professor of oncology and co-director of the Ludwig Center. The test was used on 812 healthy controls and produced only seven false-positive results.

Cristian Tomasetti, PhD, a Johns Hopkins’ associate professor of oncology and biostatistics, who developed the algorithm said the novelty of the researchers’ classification method was that it “combined the probability of observing various DNA mutations together with the levels of several proteins in order to make the final call.” “Another new aspect of our approach is that it uses machine learning to enable the test to accurately determine the location of a tumor down to a small number of anatomic sites in 83 per cent of patients.”

Although the current test does not pick up every cancer, it identifies many cancers that would likely otherwise go undetected. “Many of the most promising cancer treatments we have today only benefit a small minority of cancer patients, and we consider them major breakthroughs. If we are going to make progress in early cancer detection, we have to begin looking at it in a more realistic way, recognising that no test will detect all cancers,” says Bert Vogelstein, MD, co-director of the Ludwig Center, Clayton Professor of Oncology and Howard Hughes Medical Institute investigator.

To zero in on the analytes they included in their CancerSEEK test, the research team pulled data from more than three decades of cancer genetics research generated at their Ludwig Center at Johns Hopkins, where the first genetic blueprints for cancer were created, as well as data from many other institutions.

To precisely determine the optimal number of DNA bases to assess in the CancerSEEK test, the researchers used a method based on diminishing returns. “The more DNA bases you assay, the more mutations you are capable of finding, but eventually you reach a point of diminishing returns,” explains Cohen. “We designed our test to reflect this point of diminishing returns, including the DNA markers that were useful to detecting the cancers and eliminating those that did not add benefit.” The result was a relatively small panel of highly selective DNA markers.

“This test represents the next step in changing the focus of cancer research from late-stage disease to early disease, which I believe will be critical to reducing cancer deaths in the long term,” says Vogelstein.

CancerSEEK is noninvasive and can, in principle, be administered by primary care providers at the time of other routine blood work. “This has the potential to substantially impact patients. Earlier detection provides many ways to improve outcomes for patients. Optimally, cancers would be detected early enough that they could be cured by surgery alone, but even cancers that are not curable by surgery alone will respond better to systemic therapies when there is less advanced disease,” says Anne Marie Lennon, MD, PhD, associate professor of medicine, surgery and radiology, clinical director of gastroenterology and director of the Multidisciplinary Pancreatic Cyst Program.

The investigators said they felt that a test that will be used routinely for cancer screening must have a cost in line with, or less, than other currently available screening tests for single cancers, such as colonoscopy. They envision that the CancerSEEK test will eventually cost less than $500.

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